ClinVar

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Pro418 amino acid residue in SH3BP2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11381256, 14577811, 18596838, 21794028, 22153076, 22153077, 24916406, 25144740, 30236129). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SH3BP2 protein function. This variant has not been reported in the literature in individuals affected with SH3BP2-related conditions. This variant is present in population databases (rs757336022, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 418 of the SH3BP2 protein (p.Pro418Ala).